Cosmetic formulations for the prevention and therapy of hair loss

ABSTRACT

Formulations for the prevention and therapy of hair loss and seborrhoea are based on essential oils obtainable through alcoholic distillation of plants which contain the essential oils, combined with salicylic acid and with fatty acids having 10 to 40 carbon atoms.

The present invention provides new formulations useful in the preventionand therapy of hair loss, based on the combination of substances withvasokinetic, antibacterial and antiandrogenic activities. It is knownfrom the literature and from the cosmetic practice that the hair loss isnegatively influenced by a reduced periferic microcirculation in the“galea capitis”, by its altered relation with the bacterial flora and byan altered local androgenic methabolism. The androgens, in particularthe increased deposit of dihydrotestosterone in the hair bulb, areconsidered to play an important role in the pathogenesis of androgenicalopecia.

In Japanese patent JP-8310923, the essential oils obtained by steamdistillation of Citrus aurantium peels, and of Salvia officinalis,Mentha piperita, Eucaliptus globulus, Artemisia princeps and Rosmarinusofficinalis leaves and flowers, are considered inhibitors oftestosterone 5-alpha-reductase and therefore useful in the treatment ofalopecia, hirsutism and seborrhoea. European patent EP-433131A claimsessential oils incorporated in lipidic material in the presence of knownvasodilators like methyl nicotinate or other synthetic compounds for theprevention of hair loss or of dandruff formation, and likeantiparasites. The chemical composition of these essential oils is notreported and their effects are likely mediated by other syntheticcompounds present in the final formulations.

Now, a mixture of monoterpenes obtained through alcoholic extractionfollowed by distillation of some plants alone or in combination, hassurprisingly shown vasokinetic, antibacterial and antiseborrhoicactivities. The antibacterial activity which was known for the essentialoils, was never associated to a marked vasokinetic activity, which wasdemonstrated by the control of the blood flow in cutaneous areas treatedbefore and after the application of the mixture, using Laser Dopplertechnique and computer videocapillary-scopy.

The monoterpene mixture, combined with salicylic acid which is known tostrongly inhibit cyclooxygenase I and II, and with saturated andunsaturated fatty acids having acyl chains from 10 to 14 carbon atoms,in particular 12 carbon atoms like lauric and myristic acids, has shownparticularly useful for the treatment of hair loss in normal conditionsand in androgenic alopecia. The monoterpene mixture can be obtained bymixing the single commercial monoterpenes in suitable ratios, or betterby mixing roots, rhizomes, leaves, barks and seeds of some hexoticplants containing essential oils, which so far have never been used incosmetics for the prevention or the therapy of hair loss (with theexception of rosemary oil, the cosmetic use of which is known and it isbased on mechanisms different from those reported in the presentinvention), by steeping the same in 70% ethanol and finally bycollecting the alcohol which contains the desired monoterpens throughdistillation at room pressure.

For example, the mixture of essential oils can be obtained by steepingin 70% aqueous ethanol similar amounts of rhizomes from Curcuma longa,Myristica fragrans, Ferule galbaniflua, Liquidambar orientalis, Alpiniaofficinarum, Acorus calamus, Aloe vera, Cannarium commune, Commiphoramolmol, Eugenia aromatica, Cinnamonum cassia, Curcuma zedoaria, Arnicamontana, Rosmarinus officinalis and lower amounts of oil of turpentine,the vegetal material amount being comprised between 10 and 50 g,preferably 20 g of each plant, in 1.2 1 of 70% ethanol for two days withstirring at room temperature, then distilling the alcohol at roompressure and collecting from 0.7 to 0.95 1 of distillate, preferably0.850 lt; this distillate, after suitable water dilution, preferably upto 50% w/w, can be used as such, after removal of the insoluble oilyresidue, to inhibit hair loss or it can serve as the basis for theaddition of other active ingredients. In particular the mixture obtainedthrough distillation, combined with salicylic acid and menthol, afterdilutions with 25 to 75% w/w hydroalcoholic solutions, preferably up to50%, is steeped for a period of 3 to 60 days, preferably 30 days, and itis used after removal of insoluble oily residues.

Said hydroalcoholic mixture, which contains as the main ingredientsbeta-pinene, camphene, beta-myrcene, limonene, cineole(I,8-epoxy-p-menthane), camphor, linalool, bornyl acetate, isobornylacetate, menthol, terpinen-ol, isoborneol, in ratios corresponding tothe gas chromatogram of the Figure, is the first object of theinvention. Said chromatogram was obtained using a HP-Innowax column(cross -linked polyethylene glycol, N. of part 19091 N-133, 30 m×0.25 mmI.D., 0.25 μm film thickness), according to the following temperatureprogram: 60° C.×5 min, 60° C. to 250° C. at 3°/min, 250° C. for 3 min;injection with PTV (Programmed Temperature Vaporizer), from 120° C. to250° C. The addition to the mixture of salicylic acid or the saltsthereof and of fatty acids with anti androgenic activity, results in asurprising synergistic effect which reduces the hair loss improving thehair growth and strength. Therefore, a second object of the invention isrepresented by a formulation which contains the above described mixturein combination with salicylic acid or the salts thereof, and withsaturated or unsaturated C₁₀-C₁₄ fatty acids.

According to a preferred embodiment of the invention, the mixture ofessential oils is obtained by steeping 20 g of Curcuma zedoariarhizomes, 20 g of Myristica fragrans seeds, 20 g of Cinnamomum cassiabranch bark, 20 g of Eugenia aromatica flowers, 20 g of Acorus calamusrhizomes, 20 g of Zingiber officinalis rhizomes and 20 g of Alpiniaofficinarum, in 0.9 1 ethanol. After one day, resin oils of Ferulagalbaniflua, Liquidambar orientalis, Aloe vera, Cannarium commune,Commiphora molmol, Arnica Montana, Rosmarinus officinalis and turpentineoil are added to the steeped product in amounts variable from 5 to 50 g,to favour the alcohol dispersion of the resin oils.

Afterwards water is added up to an alcoholic grade of about 70% andafter stirring the mixture for two hours at 40° C., the distillation isstarted and about 0.85 1 of alcoholic distillate are collected. Thedistillate is a colourless clear liquid with a strongly aromatic smell.

The distillate, without the addition of other substances, hasvasokinetic, antibacterial and antiseborrhoic activities.

The monoterpene-containing hydroalcoholic mixture increases the volumeand flow-rate at the capillary level, which, as mentioned above, isextremely important in the primitive and secondary alopecia. In fact,when the mixture is applied on the cutis, it integrates the blood flowin various organic districts and in particular it increases the bloodflow in the “galea capitis” as it results from the data reported intable I, wherein the flow increment has been tested using Laser Doppler.

TABLE I Cutaneous blood flow variations determined using Laser Dopplerafter single administration of the alcoholic distillate 1:1 diluted withwater. Substances 0 30′ 60′ 90′ 120′ Distillate 4.45 13.33 14.12 9.7 10.32 Placebo 5.24  5.63  7.78 4.64  6.61

The administration of the formulations of the invention for periodsvariable from one week to three months causes in humans a remarkablereduction of androgenic alopecia as it results from the data reported intables II and III. Table II reports the flow increase caused by theapplication of the formulation of the example I, as evidenced by LaserDoppler analysis. Laser Doppler flowmetry was performed to test thevasokinetic effects, using the PeriFlux(R) PF3 flowmeter which is aninstrument emitting a subtle bundle of 632 nm wavelenght monocromaticlight, which is produced by a low potency He—Ne laser source. By thistechnique, the scalp blood flow was measured in basal conditions andafter the application of the test products, with an interval of 15 minfrom the first application (acute effect) and after 30, 60 and 90 daytreatment (chronic effect). The results are reported in table II.

TABLE II Mean blood capillary flow effects induced by the topicalapplication (90 days) of the lotion prepared according to the example I.Capillary flow (AU30 m ± e.s.) Treatment Basal 15 min 30 days 60 days 90days Alcoholic distillate 9.2 ± 1.0 23.1 ± 3.0* 11.7 ± 2.4 16.8 ± 1.2*16.7 ± 1.1* Placebo 9.4 ± 1.2 10.0 ± 1.3  10.7 ± 1.5 11.0 ± 1.1  11.5 ±0.9  Comp. lotion 9.3 ± 1.1 24.0 ± 3.1* 18.1 ± 2.5 20.1 ± 1.3* 19.4 ±1.0* *= p < 0.01 vs basal as the result of the variance analysis of asplit-plot graphic (Bonferroni's t). N = 10.

The trichograms of tested subjects randomly divided into 10 groups, wereperformed in order to evaluate the effect of the formulations on thehair loss inhibition at the beginning and at the end (90 days) of thetreatment. The trichogram consists in the withdrawal of a suitablenumber (about 50) of hairs using rubberized forceps, from thesuperior-frontal and latero-nuchal areas.

The microscopic examination of hair roots allows to evaluate the hairquantity which is in the anagen (growth), catagen (mature) and telogen(rest) phase. The reduction in the anagen percentage and the increase inthe telogen percentage, with respect to normal values (which are about85-90% and 10-15%, respectively), represent the clinical evidence of apathological hair loss.

TABLE III Trichogrammic effects induced by the topical application (90days) of the lotion prepared according to the example I Trichogram (% −m ± e.s.) Treatment telogen anagen + catagen Alc. dist. Before 76 ± 3 24± 1 After 90 days 81 ± 3 19 ± 1 Alc. dist. + Before 78 ± 2 22 ± 1 Salic.Ac. After 90 days 82 ± 2 18 ± 1 Ac. + dist. Before 74 ± 2 26 ± 2 Ac.salic. + After 90 days  86 ± 3*  14 ± 1* Fats *= p < 0.01 vs basal asthe result of the calculation.

As it comes out from the data reported above, the alcoholic distillatetopically applied for long periods, by the dayly administration of thepreparation, exerts time-persisting favourable microvasculokineticeffects on the cutis. The trichological pharameters, telogen, anagen andcatogen, behave in a similar manner. The combination of the distillatewith other substances like the low molecular weight saturated andunsaturated fatty acids, which interfere with androgen receptors, leadsto a clear improvement of the telogen-anagen-catagen ratios. The skintreatment through an increased blood flow and the consequent increase ofnutritive substances, after few days results in a clear cutaneousmodification with the increase of the number of perfused capillaries andwith dandruff absence; the hair bulbs are normal and patent, with anormal sebaceous production.

The cosmetic formulations of the invention are in the form ofhydroalcoholic lotions (which are preferred for the treatment of thescalp) or in the form of gels, and are used in the treatment of hairloss and seborrhoea.

The combinations which are preferred for the treatment comprise thehydroalcoholic mixture in a concentration between 5 and 20%, preferably10%, the fatty acids between 0.1 and 0.5%, preferably 0.25%, and thesalicylic acid between 0.1 and 1%, preferably 0.3%.

The treatment with these substances ranges from few days to six months.Examples of formulations according to the invention are hereafterillustrated but in any case they are not intended to limit theinvention.

EXAMPLE I

Preparation of the distillate having high content of essential oils,which can be used as the basis of cosmetic formulations for thetreatment of the scalp.

0.9 1 of ethanol are poured in a 2 1 beaker and 20 g of Curcuma zedoariarhizomes, 20 g of Myristica fragrans seeds, 20 g of Cinnamonum cassiabranch barks, 20 g of Eugenia aromatica flowers, 20 g of Acorus calamusrhizomes, 20 g of Zingiber officinalis rhizomes and 20 g of Alpiniaofficinarum are added (finely minced) with stirring and steeped for 1day. 10 g of Ferula falbaniflua, Liquidambar orientalis, Cannariumcommune, Commiphora molmol, Rosmarinus officinalis resin oils are addedto the steeped product without removal of the vegetal material; further,20 g of oil of turpentine are added to favour the alcohol dispersion oftherein oils. After two day steeping, water is added up to an alcoholicgrade of about 70% and after stirring the mixture for 2 hours at 40° C.,the distillation at room pressure is started and 0.85 1 of alcoholicdistillate are collected. The distillate contains as the mainconstituents beta-pinene, comphene, beta-myrcene, limonene, cineole(1,8-epoxy-p-menthane), camphor, linalool, bornyl acetate, isobornylacetate, menthol, terpinen-ol, isoborneol, according to the gaschromatogram reported in the Figure, the indicated ratios.

EXAMPLE II

Lotion containing essential oils, salicylic acid, lauric acid.

100 g of the lotion contain:

21 g distillate according to the example 1

0.3 g salicylic acid

0.2 g lauric acid

6.9 g rosemary essential oil

0.79 g Pantasol P

1.18 g Menthol

34 g Rhum aromatized alcohol

Demineralized water q.s. to 100 g

EXAMPLE III

Lotion containing essential oils, lauric acid, 80:20 mixture oftetrameric cyclosiloxane and pentameric cyclosiloxane.

100 g of the lotion contain:

21 g essential oil distillate according to the example I

0.2 g lauric acid

0.08 g camphor

15 g 80:20 mixture of tetrameric and pentameric cyclosiloxane

1.18 g menthol

What is claimed is:
 1. Hydroalcoholic mixture of beta-pinene, camphene,beta-myrcene, limonene, cineole (1,8-epoxy-p -methane), camphor,linalol, bornyl acetate, isobornyl acetate, menthol, terpinen-ol,isoborneol monoterpens, having a chromatogram as shown in the Figure. 2.Combination of the mixture of claim 1 with salicylic acid or the saltsthereof and with C₁₀-C₁₄ saturated or unsaturated fatty acids. 3.Combination according to claim 2, wherein the mixture is present in aconcentration comprised between 5 and 20% w/w, the salicylic acidbetween 0.1 and 1%, the fatty acids between 0.1 and 0.5%.
 4. Combinationaccording to claim 3, wherein said mixture is present in a concentrationof 10%, the salicylic acid in a concentration of 0.3%, the fatty acidsin a concentration of 0.25%.
 5. Cosmetic formulations containing thecombination of claim 2 in admixture with carriers and excipientspharmaceutically acceptable.
 6. Formulations according to claim 5 in theform of hydroalcoholic lotions and gels.
 7. Process for the preparationof the mixture of claim 1, which comprises the steps of: a) steeping in70% ethanol one or more parts selected from the group consisting ofroots, rhizomes, leaves, bark and seeds from Curcuma zedoaria, Myristicafragrans, Cinnamonum cassia, Eugenia aromatics, Acorus calamus, Zingiberofficinalis, Alpinia officinarum, Ferula galbaniflua, Liquidambarorientalis, Aloe vera, Cannarium commune, Commiphora molmol, Arnicamontana, Rosmarinus officinalis, together with terpentine oil, for twodays with stirring at room temperature; b) distilling the product ofstep a) at 40° C. at room pressure; and c) diluting the distillate ofstep b) with water and removing the insoluble oleous residue.
 8. Processaccording to claim 7 wherein the plants or the parts thereof are used inamounts comprised between 10 and 50 g for each plant.
 9. Processaccording to claim 8, wherein the amount is 20 g.
 10. Hydroalcoholicmixture obtainable by the process of claim
 7. 11. A method for thetreatment of hair loss and of seborrhoea comprising applying to a humanscalp a cosmetic formulation prepared from the hydroalcoholic mixture ofclaim 1, as such or in combination with salicylic acid or the saltsthereof and with C₁₀-C₁₄ saturated or unsaturated fatty acids. 12.Cosmetic formulations containing the combination of claim 3 in admixturewith carriers and excipients pharmaceutically acceptable.
 13. Cosmeticformulations containing the combination of claim 4 in admixture withcarriers and excipients pharmaceutically acceptable.
 14. Formulationsaccording to claim 12, in the form of hydroalcoholic lotions and gels.15. Formulations according to claim 13, in the form of hydroalcoholiclotions and gels.